Skin sodium buildup and outcomes in people with chronic kidney disease

The Role of Skin Sodium Accumulation in Chronic Kidney Disease

This project will test whether skin sodium levels change with different diets, medicines, and water intake and whether those levels link to kidney and heart outcomes in adults with chronic kidney disease (eGFR 15–60).

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Academic / other)
• Locations: 1 site (Amsterdam-Zuidoost, North Holland)
• Trial ID: NCT07020104 on ClinicalTrials.gov

What this trial studies

This project enrolls a cohort of CKD patients and uses sodium MRI to measure tissue sodium and study its relationship with vascular function, quality of life, and future renal and cardiovascular events. Nested randomized cross-over interventions will test the effects of short-term high vs low dietary sodium, diuretic and antihypertensive regimens to increase renal sodium excretion, and changes in water intake on tissue sodium content. The cohort includes up to 60 patients, with smaller randomized subgroups for each intervention arm. Patients are followed for clinical events while imaging and physiologic measures are repeated to link changes in tissue sodium with functional and clinical outcomes.

Who should consider this trial

Good fit: Adults with chronic kidney disease and an eGFR between 15 and 60 ml/min/1.73 m2 who have been on stable diuretic and antihypertensive therapy for at least six weeks are the intended participants, with specific subgroups for hypertension or low urine osmolality as required for the interventions.

Not a fit: Patients with rapidly progressing disease, planned imminent dialysis or transplant, active nephrotic syndrome, recent glomerulonephritis, salt-wasting disorders, or on higher-dose glucocorticoids are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the findings could help personalize sodium, fluid, and blood-pressure management to lower kidney and cardiovascular risk in people with CKD.

How similar studies have performed: Prior small studies using sodium MRI have linked tissue sodium to blood pressure and heart failure, but applying dietary, pharmacologic, and water interventions and linking tissue sodium to long-term CKD outcomes is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m2.
2. Stable diuretic and antihypertensive treatment for the previous 6 weeks.

Additional inclusion criteria for the sodium excretion intervention 1. Office systolic blood pressure (SBP) \>135 mmHg

Additional inclusion criteria for the water intervention

1. Chronic kidney disease with an eGFR between 15 and 29 ml/min/1.73m2
2. Office blood pressure ≥140/90 mmHg or use of antihypertensive medication
3. Fasting morning urine osmolality \<425 mOsm/kg for men and \< 400 mOsm/kg for women

Exclusion Criteria:

1. Age \<18 years.
2. The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months.
3. An active diagnosis of nephrotic syndrome at inclusion.
4. (Recurrent) acute glomerulonephritis within 1 year prior to the study.
5. Salt losing nephropathy.
6. Use of oral or intravenous glucocorticoids with an equivalent of prednisolone \>5mg/day.
7. Contra-indication for MRI.
8. Cardiovascular event/ surgery in the previous 3 months.
9. Pregnant women, women of child bearing age planning to conceive for the study duration, women of child bearing age without contraception.
10. Participation in other (pharmacological) intervention studies.
11. Presence of significant comorbidities with a life expectancy of less than 1 year.
12. Disorder that compromises the participants' ability to give truly informed consent for participation in this study.
13. Patients with an active infection and/or auto-immune diseases with involvement of the lower extremities.
14. Any other issues that in opinion of the investigator could be harmful to the subject or compromise interpretation of the data.

Additional exclusion criteria for the sodium intake intervention

1\. Chronic use of NSAID

Additional exclusion criteria for the sodium excretion intervention

1. Serum potassium concentration \>5.0 mmol/l.
2. eGFR \<30 ml/min/1.73m2
3. Uncontrolled hypertension (\>180/100 mmHg)
4. Severe heart failure with left ventricular ejection fraction \<30%.
5. Contra-indication for investigational drugs.
6. Severe symptoms of (orthostatic) hypotension.
7. Patients with obstruction of the outflow tract of the left ventricle such as aortic valve stenosis.
8. Refractory hypokalemia, hyponatremia or hypercalcemia.
9. Severe liver insufficiency Child Pugh B/C
10. Chronic use of NSAID.

Additional exclusion criteria for the water intake intervention

1. Recent history of severe hyponatremia (outpatient plasma sodium \< 130 mmol/L in the last 6 months)
2. Plasma sodium \<135 mmol/L at screening
3. History of heart failure
4. Use of lithium, vasopressin analoga, vasopressin antagonists, oral or intravenous glucocorticoids, thiazide diuretics.
5. 24-hour urine volume \> 2L
6. Chronic use of NSAID

Where this trial is running

Amsterdam-Zuidoost, North Holland

• Amsterdam UMC — Amsterdam-Zuidoost, North Holland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Rik Olde Engberink, MD, PhD — Amsterdam UMC, location AMC
• Study coordinator: Rik Olde Engberink, MD, PhD

Conditions Chronic Kidney Diseases; Skin sodium; Sodium MRI; CKD; Prognosis; Cardiovascular event; Renal event; Quality of life